S. Aureus - antibiotic resistance


It has been suggested that people exposed to land applied sewage sludge
may be at increased risk of infection by S. Aureus. Here is a news
story about antibiotic resistance and S. Aureus.



VRSA: The Worst Has Finally Happened

Charles 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 GlaxoSmithKline, 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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Staphylococcus aureus resistant to vancomycin -- United States, 2002.
MMWR. Morb Mortal Wkly Rep. 2002;51:565-567.
Full text: http://www.medscape.com/viewarticle/438138
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