VRE Article

[Guest guest]

VRSA: The Worst Has Finally Happened

Stratton, MD Disclosures

San Diego, Friday, September 27, 2002 -- The first day of the 42nd ICAAC

was highlighted by several reports of new mechanisms of resistance in

Staphylococcus aureus. These newly described mechanisms are likely to be

of great importance to the practicing physician because of the

importance of S aureus as a human pathogen.[1,2] In the late-breaker

slide session, D.M. Sievert and colleagues[3] from the Michigan

Department of Community Health, Lansing, Michigan and the Centers for

Diseases Control and Prevention (CDC), Atlanta, Georgia, reported the

details of the first case of vancomycin-resistant S aureus (VRSA)

infection. The CDC briefly reported on this strain in July.[4] In the

following presentation, J.M. Mohammed and associates[5] from the CDC

characterized this strain. The development of vancomycin resistance in

this organism, the worst fear of infectious diseases practitioners,

finally has occurred. Moreover, in an ICAAC Program Committee Award

Presentation, J. Huang and colleagues[6] from GlaxoKline,

Collegeville, Pennsylvania, reported the identification of a novel

multidrug resistance system (MdeA) from S aureus.

What do these reports mean to the practicing physician? Let us first

briefly review the history of antimicrobial resistance in this common

pathogen.

S aureus was first recognized in the late 1800s as a common cause of

infection. In the preantimicrobial era, it carried a bacteremia

mortality rate of 82%.[1,2,7] The use of penicillin, one of the first

antimicrobial agents developed in the 1940s, markedly reduced this high

mortality rate.[8] However, the occurrence of staphylococcal strains

producing penicillinase was seen almost simultaneously with the

introduction of penicillin.[9] Prior to 1940, 90% of all S aureus

isolates were susceptible to penicillin. By 1952, 75% of isolates

displayed beta-lactamase-mediated resistance.[10] The antimicrobial

therapy of staphylococcal infections has remained a problem due to the

rapid emergence of multiple mechanisms of resistance.[11-13] Similarly,

rapid emergence of resistance to penicillin derivatives that were

designed to be resistant to staphylococcal beta-lactamase, such as

methicillin, was seen in the 1970s.[14] Shortly after the introduction

of fluoroquinolones in the 1980s, rapid emergence of resistance to these

agents was seen due to altered topoisomerases as well as efflux

mechanisms.[15,16]

Throughout this evolution of multidrug-resistant strains of S aureus,

vancomycin has remained the mainstay of antimicrobial therapy for

resistant strains ever since its introduction in the mid-1950s.[17]

Indeed, clinical experience has suggested that the development of

resistance to vancomycin by S aureus was difficult, despite the

occasional reports of low-level resistance.[18,19] The laboratory in

vitro demonstration in 1992 that the van resistance genes from

enterococci could be transferred to S aureus and expressed, thus

producing vancomycin resistance,[20] was of great concern, but to date

such a transfer had not been reported in wild strains. But with these

reports, the unthinkable has happened.

This newly reported VRSA was isolated from the catheter tip of a renal

dialysis patient in Michigan. The isolate contained both the mecA gene

for methicillin resistance and the vanA gene for vancomycin resistance.

MICs were 1024 mcg/mL to vancomycin and 32 mcg/mL to teicoplanin,

consistent with the vanA phenotype of enterococcus.[21] The presence of

the vanA gene was confirmed by PCR and was located on a 60-kb plasmid.

The DNA sequence of the VRSA vanA gene was identical to that of a

vancomycin-resistant strain of Enterococcus faecalis recovered from the

same catheter tip culture. The isolate was, however, susceptible to

trimethoprim/sulfamethoxazole, minocycline, linezolid, and

quinupristin/dalfopristin. This VRSA is, thus, the first likely transfer

in vivo of high-level vancomycin resistance from E faecalis to S aureus.

Should this plasmid, or another one like it, be transferred from one S

aureus strain to another as rapidly as was the plasmid containing the

beta-lactamase gene,[10] this report may herald the demise of vancomycin

as a clinically useful agent.

The importance of the newly characterized efflux mechanism is not that

it confers resistance against any particular antimicrobial agent. In

fact, this efflux pump resistance mechanism was not very impressive in

the type of resistance it conferred. However, this is the second of an

estimated 12-15 efflux pump resistance mechanisms that S aureus strains

are thought to have. One of these efflux mechanisms in the future could

mutate so that it conferred resistance to drugs such as minocycline,

linezolid, and quinupristin/dalfopristin.

Once again, S aureus has demonstrated its propensity to become resistant

despite attempts to develop new antistaphylococcal agents. The future

for the therapy of serious staphylococcal infections looks bleak,

indeed.

References

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Full text: http://www.medscape.com/viewarticle/438138

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Becki

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