New MRSA Superbug Emerges in Brazilian Patient - VRSA

[Gert van der Hoek]

New MRSA Superbug Emerges in Brazilian Patient

By Bahar Gholipour, Staff Writer | April 17, 2014

A new, highly drug-resistant type of the superbug methicillin-resistant Staphylococcus aureus (MRSA) recently caused a fatal blood infection in a Brazilian patient, according to a new report.

The 35-year-old man, who was in poor health and had been in the hospital for a long time, was infected with a strain of MRSA that developed resistance — during his hospital stay — to the powerful antibiotic vancomycin, which is widely used to treat this infection.

Researchers found that unlike previous superbugs that were associated with hospitals, this vancomycin-resistant staph bacteria (VRSA) is genetically related to a MRSA strain that has been circulating in the United States and northern South America, according to the study, published today (April 17) in the New England Journal of Medicine.

Live Science


N Engl J Med 2014; 370:1524-1531April 17, 2014DOI: 10.1056/NEJMoa1303359

Transferable Vancomycin Resistance in a Community-Associated MRSA Lineage

We report the case of a patient from Brazil with a bloodstream infection caused by a strain of methicillin-resistant Staphylococcus aureus (MRSA) that was susceptible to vancomycin (designated BR-VSSA) but that acquired the vanA gene cluster during antibiotic therapy and became resistant to vancomycin (designated BR-VRSA).

Both strains belong to the sequence type (ST) 8 community-associated genetic lineage that carries the staphylococcal chromosomal cassette mec (SCCmec) type IVa and the S. aureus protein A gene (spa) type t292 and are phylogenetically related to MRSA lineage USA300. A conjugative plasmid of 55,706 bp (pBRZ01) carrying the vanA cluster was identified and readily transferred to other staphylococci. The pBRZ01 plasmid harbors DNA sequences that are typical of the plasmid-associated replication genes rep24 or rep21 described in community-associated MRSA strains from Australia (pWBG745).

The presence and dissemination of community-associated MRSA containing vanA could become a serious public health concern.


The Lancet. First case of infection with vancomycin-resistant Staphylococcus aureus in Europe

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[mixin]

Re: New MRSA Superbug Emerges in Brazilian Patient - VRSA

Published Date: 2014-04-22 15:50:25
Subject: PRO/EDR> Staphylococcus aureus, MRSA - Brazil: (SP) vancomycin resistant (VRSA) update
Archive Number: 20140422.2420131
STAPHYLOCOCCUS AUREUS, MRSA - BRAZIL: (SAO PAULO) VANCOMYCIN RESISTANT (VRSA) UPDATE
************************************************************************************
A ProMED-mail post
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International Society for Infectious Diseases
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Date: Thu 17 Apr 2014
Source: The Global Dispatch [edited]
http://www.theglobaldispatch.com/vancomycin-resistant-mrsa-superbug-found-in-brazil-87829/


An international research team led by Cesar A Arias, MD, PhD, at The University of Texas Health Science Center at Houston (UTHealth) has identified a new superbug that caused a bloodstream infection in a Brazilian patient. The report appeared in the [17 Apr 2014] issue of The New England Journal of Medicine.

The new superbug is part of a class of highly-resistant bacteria known as methicillin-resistant _Staphylococcus aureus _or MRSA, which is a major cause of hospital and community-associated infections. The superbug has also acquired high levels of resistance to vancomycin, the most common and least expensive antibiotic used to treat severe MRSA infections worldwide.

Most worrisome is that genomic analyses indicated that this novel vancomycin-resistant MRSA superbug belongs to a genetic lineage that is commonly found outside hospitals (designated community-associated MRSA), said Arias, the report's senior author and an associate professor of medicine, microbiology, and molecular genetics at the UTHealth Medical School.

Previous research has suggested that community-associated MRSA can disseminate rapidly among people and is responsible for the majority of skin and soft tissue infections (sores) in patients of all ages. Some of these infections can become serious and even fatal.

Since community-associated MRSA is thought to be transmitted mainly by skin contact, the new superbug may affect not only sick people or those with a weakened immune system but also healthy individuals, according to Arias. Apart from causing localized skin infections, the MRSA superbug has the ability to invade the bloodstream and may become a serious threat.

"This is the 1st-ever reported bloodstream infection caused by a highly vancomycin-resistant MRSA bacterium," Arias said. "If we lose vancomycin, it would make it very difficult and expensive to treat these infections," he said.

Arias and his colleagues conducted microbiological and genetic analyses of an MRSA superbug recovered from the blood of a 35-year-old Brazilian man and identified a novel transferable genetic element (plasmid) that carries the genes necessary for vancomycin resistance (_vanA_ gene cluster).

"The presence and dissemination of community-associated MRSA containing _vanA_ could become a serious public health concern," report the authors in the paper.

However, since this is the only documented case of this type of infection, Arias said, it is too early to tell if this specific superbug will lead to a bigger threat.

Barbara E Murray, MD, report co-author and director of the Division of Infectious Diseases at the UTHealth Medical School, said, "The worst resistance possible has now appeared in the community-associated MRSA clone."

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[The news report above refers to a study recently published in the New England Journal of Medicine, which is a follow-up of studies previously posted by ProMED-mail (Staphylococcus aureus, MRSA - Brazil: (SP) vancomycin resistant (VRSA) 20130630.1800166):
Rossi F, Diaz L, Wollam A, Panesso D, et al: Transferable Vancomycin Resistance in a Community-Associated MRSA Lineage. N Engl J Med 2014; 370(6): 1524-31. doi: 10.1056/NEJMoa1303359. The abstract, reproduced below, is available at http://www.nejm.org/doi/full/10.1056/NEJMoa1303359:

"We report the case of a patient from Brazil with a bloodstream infection caused by a strain of methicillin-resistant _Staphylococcus aureus_ (MRSA) that was susceptible to vancomycin (designated BR-VSSA) but that acquired the _vanA_ gene cluster during antibiotic therapy and became resistant to vancomycin (designated BR-VRSA). Both strains belong to the sequence type (ST) 8 community-associated genetic lineage that carries the staphylococcal chromosomal cassette mec (SCCmec) type IVa and the _S. aureus_ protein A gene (spa) type t292 and are phylogenetically related to MRSA lineage USA300. A conjugative plasmid of 55 706 bp (pBRZ01) carrying the _vanA_ cluster was identified and readily transferred to other staphylococci. The pBRZ01 plasmid harbors DNA sequences that are typical of the plasmid-associated replication genes rep24 or rep21 described in community-associated MRSA strains from Australia (pWBG745). The presence and dissemination of community-associated MRSA containing _vanA_ could become a serious public health concern."

In the past 12 years 13 isolates of vancomycin-resistant _Staphylococci aureus_ (VRSA) have been reported in the US. VRSA appears often to arise in vivo in settings where vancomycin-resistant enterococci (VRE) and methicillin-resistant _Staphylococci aureus_ (MRSA) are both present in the patient. All VRSA have been MRSA that have acquired the _vanA_ gene cluster by horizontal gene transfer from vancomycin-resistant enterococci (VRE). The _vanA_ gene cluster is carried on a plasmid and determines high-level vancomycin resistance.

MRSA are characterized genotypically by pulsed-field gel electrophoresis (PFGE) patterns, protein A (spa) gene typing, carriage of Panton-Valentine leukocidin (PVL) genes, multilocus sequence typing (MLST), and the type of staphylococcal chromosomal cassette mec (SCCmec) element carried. MRSA are grouped into clonal complexes by MLST, which contain genetically related ST types. The mecA gene, which determines resistance to all beta-lactams, including methicillin, is localized on a mobile genetic element SCC, which was likely acquired from a coagulase-negative staphylococcus species.

Of the 13 VRSA in the US, 12 belonged to clonal complex 5, encompassing both the USA100 and USA800 PFGE types, a lineage associated primarily with MRSA acquired in healthcare settings (HA-MRSA). The 13th isolate, however, belonged to clonal complex 30, USA1100, a lineage associated with MRSA acquired in community settings (CA-MRSA) (http://jcm.asm.org/content/52/3/998.abstract).

The usual HA-MRSA strains carry a relatively large SCCmec belonging to type I, II, or III. HA-MRSA are often resistant to other classes of non-beta-lactam antimicrobials and strains seldom carry the PVL genes. In contrast, CA-MRSA isolates carry smaller the SCCmec elements, SCCmec type IV or type V. They are resistant to fewer non-beta-lactam classes of antimicrobials and frequently carry PVL genes.

Although USA300 is the predominant PFGE type in community-associated MRSA, USA300 is also emerging as an important cause of healthcare-associated infections. USA300 causes skin and soft tissue infections (SSTI), but is responsible for rapidly progressive, fatal infections including necrotizing pneumonia, severe sepsis and necrotizing fasciitis, and more recently the types of infections that HA-MRSA typically cause, for example, septic arthritis, endocarditis, osteomyelitis, foreign-body infections, and sepsis.

The current NEJM article, to which the news report above refers, describes acquisition of the _vanA_ gene cluster by an invasive bloodstream MRSA isolate that belongs to the predominant community-associated MRSA lineage, clonal complex 8, USA 300 in a patient at a Brazilian hospital. Acquisition of vancomycin resistance by the MRSA likely happened in vivo during the administration of the glycopeptide antibiotics vancomycin and teicoplanin to this patient.

Because USA300 has spread rapidly and replaced other MRSA lineages in both the hospital and the community, acquisition of high-level vancomycin resistance by a MRSA USA300 raises the possibility that vancomycin resistant MRSA may disseminate rapidly and replace vancomycin-susceptible MRSA lineages. - Mod.ML

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